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So far, few studies have adequately accounted for the male reproductive system responses to LDR, particularly the regulation of testosterone content. Hence, this study was designed to evaluate the effects of LDR on Leydig cells and testicular tissue, especially the ability to synthesize testosterone. We found that less than 0.2\u2010Gy <jats:sup>60<\/jats:sup>Co gamma rays did not cause significant changes in the hemogram index and the body weight; also, pathological examination did not find obvious structural alterations in testis, epididymis, and other radiation\u2010sensitive organs. Consistently, the results from in vitro showed that only more than 0.5\u2010Gy gamma rays could induce remarkable DNA damage, cycle arrest, and apoptosis. Notably, LDR disturbed the contents of testosterone in mice serums and culture supernatants of TM3 cells and dose dependently increased the expression of 3\u03b2\u2010HSD. After cotreatment with trilostane (Tril), the inhibitor of 3\u03b2\u2010HSD, increased testosterone could be partially reversed. Besides, DNA damage repair\u2010related enzymes, including DNMT1, DNMT3B, and Sirt1, were increased in irradiated TM3 cells, accompanying by evident demethylation in the gene body of <jats:italic>3\u03b2\u2010HSD<\/jats:italic>. In conclusion, our results strongly suggest that LDR could induce obvious perturbation in the synthesis of testosterone without causing organic damage, during which DNA demethylation modification of <jats:italic>3\u03b2\u2010HSD<\/jats:italic> might play a crucial role and would be a potential target to prevent LDR\u2010induced male reproductive damage.<\/jats:p>","DOI":"10.1002\/jat.4237","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T03:53:20Z","timestamp":1644810800000},"page":"529-539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Low\u2010dose radiation\u2010induced demethylation of <i>3\u03b2\u2010HSD<\/i> participated in the regulation of testosterone content"],"prefix":"10.1002","volume":"42","author":[{"given":"Cong\u2010Shu","family":"Huang","sequence":"first","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"},{"name":"School of Traditional Chinese Medicine Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Zhen","family":"Qiu","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6318-9627","authenticated-orcid":false,"given":"Lanxin","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning\u2010Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"},{"name":"School of Traditional Chinese Medicine Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Fang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Hao","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeng\u2010Chun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1131-5326","authenticated-orcid":false,"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"},{"name":"School of Traditional Chinese Medicine Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13142"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.05.057"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22341"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-020-12334-2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-019-05096-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2018.04.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.11.020"},{"issue":"1","key":"e_1_2_8_9_1","first-page":"43","article-title":"Hormonal status of male reproductive system: Androgens and estrogens in the testis and epididymis. 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